title: Low doses of ionizing radiation induce immune-stimulatory responses in isolated human primary monocytes.
abstract: The health effects arising from exposure to low doses of ionizing radiation are of particular concern, mainly due to the increased application of diagnostic and therapeutic X-ray modalities. The mechanisms behind the cell and tissue responses to low doses remain to be elucidated. Accumulating evidence suggests that low doses of ionizing radiation induce activation of the immune response; however, the processes involved have yet to be adequately investigated. Monocytes are key players in the induction of an immune response. Within the context of this study, we investigated the activation of toll-like receptors (TLRs), mitogen‑activated protein kinases (MAPKs) and NF-κB signaling in isolated human primary monocytes in response to low doses (0.05 and 0.1 Gy) and a high dose (1 Gy) of ionizing radiation. Using quantitative RT-PCR and ELISA techniques, our results showed a positive regulation of TLR signaling in response to low doses but a less significant response at high doses. This activation was demonstrated via the activation of TLR signaling molecules (HMGB1, TLR4, TLR9, MyD88 and IRAK1). Furthermore, and in contrast to the high dose, the low doses showed increased phosphorylation levels of the protein IκBα, and therefore positive signaling of the NF-κB pathway. This result denotes pro-survival and pro-inflammatory responses. Additionally, MAPKs were activated in response to 0.05 Gy, while 0.1 and 1 Gy showed a downregulatory trend that may be related to activation of the PF4 gene. On the other hand, there was highly significant involvement of activated p53 and damaged genes in response to high but not low doses. In conclusion, this study addressed the need to re-evaluate health risks arising from exposure to low doses of ionizing radiation, particularly in view of the accumulating evidence reporting inflammatory and oncogenic consequences from these exposures.
authors.affiliation: Radiobiology Unit, Molecular and Cellular Biology, Belgian Nuclear Research Centre (SCK‑CEN), 2400 Mol, Belgium.
authors.forename: Houssein
authors.initials: H
authors.lastname: El-Saghire
authors.forename: Arlette
authors.initials: A
authors.lastname: Michaux
authors.forename: Hubert
authors.initials: H
authors.lastname: Thierens
authors.forename: Sarah
authors.initials: S
authors.lastname: Baatout
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D059447:Cell Cycle Checkpoints / Q000528:radiation effects; D002469:Cell Separation; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D015536:Down-Regulation / Q000528:radiation effects; D004789:Enzyme Activation / Q000528:radiation effects; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D009000:Monocytes / Q000276:immunology* / Q000528:radiation effects*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000528:radiation effects; D010978:Platelet Factor 4 / Q000235:genetics / Q000378:metabolism; D011839:Radiation, Ionizing; D015398:Signal Transduction / Q000528:radiation effects; D051193:Toll-Like Receptors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D024243:HMGB1 Protein; D016328:NF-kappa B; D051193:Toll-Like Receptors; D016159:Tumor Suppressor Protein p53; D010978:Platelet Factor 4; D020928:Mitogen-Activated Protein Kinases